Abstract

Highly pathogenic avian influenza A/H5N1 virus can cause morbidity and mortality in humans but thus far has not acquired the ability to be transmitted by aerosol or respiratory droplet ("airborne transmission") between humans. To address the concern that the virus could acquire this ability under natural conditions, we genetically modified A/H5N1 virus by site-directed mutagenesis and subsequent serial passage in ferrets. The genetically modified A/H5N1 virus acquired mutations during passage in ferrets, ultimately becoming airborne transmissible in ferrets. None of the recipient ferrets died after airborne infection with the mutant A/H5N1 viruses. Four amino acid substitutions in the host receptor-binding protein hemagglutinin, and one in the polymerase complex protein basic polymerase 2, were consistently present in airborne-transmitted viruses. The transmissible viruses were sensitive to the antiviral drug oseltamivir and reacted well with antisera raised against H5 influenza vaccine strains. Thus, avian A/H5N1 influenza viruses can acquire the capacity for airborne transmission between mammals without recombination in an intermediate host and therefore constitute a risk for human pandemic influenza.

Links

Publisher Full Text

Authors

Herfst S, Schrauwen EJ, Linster M, Chutinimitkul S, de Wit E, Munster VJ, Sorrell EM, Bestebroer TM, Burke DF, Smith DJ, Rimmelzwaan GF, Osterhaus AD, Fouchier RA

Institution

Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.

Source

Science (New York, N.Y.) 336:6088 2012 Jun 22 pg 1534-41

MeSH

Air Microbiology
Amino Acid Substitution
Animals
Antiviral Agents
Containment of Biohazards
Disease Models, Animal
Female
Ferrets
Hemagglutinin Glycoproteins, Influenza Virus
Humans
Immune Sera
Influenza A Virus, H5N1 Subtype
Influenza in Birds
Influenza, Human
Molecular Sequence Data
Mutagenesis, Site-Directed
Mutation
Orthomyxoviridae Infections
Oseltamivir
Pandemics
Poultry
RNA Replicase
Reassortant Viruses
Receptors, Virus
Respiratory System
Reverse Genetics
Serial Passage
Sialic Acids
Viral Proteins
Virulence
Virus Replication
Virus Shedding

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22723413